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The Vets First podcast is a research-based podcast that focuses on the VA healthcare system and its patients. Instead of being just another research podcast, the Vets First podcast was created with a primary focus on the Veterans and their stories. The hosts, Levi Sowers PhD, and Brandon Rea work to bridge the gap between the state-of-the-art research being performed at Veterans Affairs and the Veterans themselves in an easy-to-understand manner. Importantly, Levi and Brandon want to assist researchers around the country to better understand the needs of Veterans. In this podcast you will hear interviews from Veterans with specific conditions and then hear from VA funded researchers who are studying those very topics as well as other highlighted services the VA provides.
The Department of Veterans Affairs does not endorse or officially sanction any entities that may be discussed in this podcast, nor any media, products or services they may provide.
Announcer: Welcome to the Vets First Podcast, a research-based conversation centered around the VA health care system, its services, and patients. From Iowa city, Iowa, here's your hosts: Dr. Levi Sowers and Brandon Rea.
Levi Sowers: Welcome back to the Vets First Podcast! Today, we're lucky to have Dr. Gramlich. He is a German born research health science specialist here at the Iowa City VA Health Care Center and a research assistant professor at the University of Iowa, as well as a research assistant professor in the neuroscience and pharmacology program. Welcome to the Vets First Podcast.
Oliver Gramlich: Yeah, thank you very much for the introduction. Happy to be here and happy to chat about some AI related research.
Levi Sowers: First and foremost. Oliver, you're German born. How where did you grow up and how did you make it to where you're at right now?
Oliver Gramlich: Well, this is a, this is a great question. So, yeah, let's start let's start back in Germany. So I, I was raised and grew up in Germany in the Frankfurt area in the former western part of Germany and I went to grad school at the University of Mainz where I studied biology as well as as ophthalmology, so eye diseases, and earned my Ph.D. there. And then I was recruited to the universe at U of Iowa to work here as a as a research scientist at the Department of Ophthalmology, basically focusing on on mom. So glaucoma related vision loss. And from there on, since glaucoma has a lot to do with the optic nerve. I also am interested in in other diseases that cause vision loss because the optic nerve gets injured. For example, like multiple sclerosis, optic nerve riders, the auto immune mediated disorders, as well as traumatic disorders like, for example, traumatic blast injury, which has also a huge impact on on optic nerve function and vision.
Levi Sowers: So I know you personally, because we work in the same center at the center of this event for the for the prevention and treatment of visual loss. And so I know a little bit more about you, so I'm going to try a little bit more back into your background. So I believe that you did some military service in Germany?
Oliver Gramlich: Mm hmm. Yeah. At the time. We need to service. That's correct. And I choose to serve as a paramedic for two years. So during my regular service time and then I stick to it for, another ten years of doing nightshift and in the EMS while going to the university during the day. So it was a very, very tough but interesting time.
Levi Sowers: So when when did you what years did you serve?
Oliver Gramlich: From 98 to 2008, probably full service and then volunteer service till 2014 when I came to Iowa.
Levi Sowers: Nice. So. So it's a little bit different in Germany. You have to serve for two years, is that correct?
Oliver Gramlich: Yeah, that was kind of the transition. So between 13 months and two years was the regular timeframe. Yeah. And you could you have the choice to serve either in the, in the, in the educational sector, in the military, a firefighter or paramedic. So and I chose I chose the paramedic, the paramedic service.
Levi Sowers: Very nice. And then so why did you end up choosing to come to Iowa, of all places?
Oliver Gramlich: Well, that was after I finished my ph.D, a researcher here at Iowa, which I which I met in 2008, Dr. Marcus (sp?). He and I, we worked on the same stuff during that time. And we met at several conferences, talked about science, talked about the next cool experiment to do. And finally he invited me, as I was looking for for new challenges and new opportunities if I wanted to, to come and join his lab, which I did. And I'm glad that I did it because that was for me. Research was a huge step forward. So many opportunities with good ideas that we had and was an amazing time. And he also helped me significantly to my way forward to independence and launched my own research project, which is, of course slightly different from his. But we are all looking at the same problems that is vision loss to various different- for various different reasons.
Levi Sowers: So all of our. What drew you to vision research and working with the VA?
Oliver Gramlich: Yeah, the VA center pretty much offered also the platform for me to, to develop a kind of independent research path. So with, with for example, sponsoring a pilot pilot project that also is in aligned with the mission of our center, which is prevention and treatment of loss of vision loss. And I was heavily focused on I'm still heavily focused on neuro ophthalmology now. So the pretty much the the link between neuroscience vision and vision loss. And that was something that was underrepresented here, at least from from the research or the preclinical side. So it was a it was a need here to to go into that research and I was the right person to do it. And I think this is a this was an amazing collaboration from the beginning on, and it was very fruitful. We received a grant funding here from the VA to to really dive deep into into that problem. And so I would say to us it was an opportunity and I grew with that opportunity and I'm super happy to be here and work work with the VA.
Levi Sowers: So very nice. You know, one thing I want to point out is that you've got an awesome accent and you're probably have one of the best accents on the podcast.
Brandon Rea: Yeah.
Oliver Gramlich: The best foreign accent.
[laughter]
Brandon Rea: We all, we only have our best Midwestern accents to work with. So-
Levi Sowers: But it makes you sound very distinguished.
Oliver Gramlich: I try my best.
Levi Sowers: That's awesome. So, yeah, you know, getting back on topic here, the what what is the importance to you of research? So you do preclinical research, meaning that you work in mice and maybe rats? I'm not exactly sure, but I think that. What would you tell a veteran that asks you why work in mice when vision loss is a human problem?
Oliver Gramlich: Yeah, I mean, this is a this is a super great question. Research starts at one point and that is that is a preclinical research. So first so my my lab is focusing on two different different things. The first thing is we need models, systems that could be mice or rats, that could be organs, that could be organ donor cells, that could be cells, it could be a whole variety. But one major focus is to investigate or to decipher the puzzle biology of certain eye diseases. And if you know how those eye diseases work in a dish or in a mouse or in a rat, the next big step is and which is, in my opinion, much more important, is how can we translate that knowledge to the human disease, to human eye diseases, in order to find new treatments? And that's the ultimate goal. So my research is highly, highly translationable between what we see in the ophthalmology clinic or what an eye doctor sees. And what I do here in the lab is pretty much to simulate those conditions in in a dish or an animal so that we can actually understand what's going on and find the right point where we can leverage new treatments.
Levi Sowers: Yeah, I think that's the big difficulty. As a translational neuroscientist, would you I would qualify you as and and be as branded as you know, I think it's important for us and it's critical for us actually to be able to say why is this important to human health? And, you know, you hit the nail on the head. I think that when you look at translational science, we take model organisms such as mice and in other models, such as cultured cells and we can do things to them that we can't do in humans. We can, you know, test certain drugs in a preclinical setting that ultimately ends up in humans. I think that's really the critical step that I think some people miss. Sometimes when we talk about our research and it's it's important for us to be able to communicate that in a way that people can understand, right?
Oliver Gramlich: That's absolutely correct. That's exactly true to the point. First, of course, we want to see if, for example, a new treatment is effective in glaucoma to save vision or to restore vision or is a new compound is effective on mitigating optic neuritis, visual loss or traumatic blast injury loss and restoring vision is probably the ultimate goal. Yes. And we want to do this first in in a dish or in an animal to see if it works, how it works, if it is safe. That's a huge thing. Before we move, we move into into a clinical practice and actually test this in in people.
Brandon Rea: So Oliver, with all of the vision problems that people or veterans have experienced like you have the eye of the optic nerve between like the eye, the the cornea, the optic nerve. What made you want to focus on the optic nerve itself?
Oliver Gramlich: The optic nerve is really the, in my opinion, the most important part of of the eye and the vision process. And if you would ask an eye doctor, the eye doctor would say, hey, yeah, the brain is an attachment to the eye. If you ask a lawyer scientist, the neuroscientists would say the eyes, just an attachment of the brain. But hold on.
Levi Sowers: Why did you give us that?
Oliver Gramlich: If you look at- think about the eye or the retina, is the only a nerve plexus, the only neurons that you can see from the outside. Yeah. So if you look into the eye, you can actually see neurons here. And I think the most important thing is the optic nerve, because it, it wouldn't work without the optic nerve to get an image from the retina to the brain. And you can have a fully functional brain. A fully functional retina is the cable. So the optic nerve doesn't work.
Brandon Rea: Yeah, I get that.
Oliver Gramlich: It's a fuzzy image. That is why I'm particularly interested in optic nerve. So.
Brandon Rea: I mean, I would joke that my brain is built into my stomach in order to get fed. So having that type of view is pretty good.
[laughter]
Levi Sowers: So the optic nerve, when we're talking about vision, you know, you receive visual input through your retina and the retina sends it through your optic nerve to your brain. Right. And that's like the main you call it the main cable, which is really what it is. It sends all the information to the back of our brain or wherever in our brain. Pathways are well known. You don't need to go over them, but it's what carries the signal to our brain. So we can see things, right?
Oliver Gramlich: That's absolutely correct. And it's like old school television. If your cable from the antenna is broken, you don't have a good image.
Levi Sowers: You know? So these- this optic nerve, I'm a little naive to it, actually. So the retina is a layer of cells. Um, some of them detect light, some of them do other things. But is it the projections from the retina that form the optic nerve, or is the optic nerve a difference of cells?
Oliver Gramlich: The optic nerve is a unique, a unique structure. And you started at the right point. So we have cells in the retina that detect light and can transform light into an electrical current. If you would describe it as that. And then that electric current or that signal gets transmitted to another cell in the retina processed and then transmitted the signal to the retina ganglion cells, Retinal ganglion cells, they they live in the retina, and these are the cells that form an axon. And that axon actually exits the eye and forms the axon of the optic nerve. So and then it runs all the way through the optic nerve to the chiasm, where the fiber is partially crossed and then into the brain. So the whole retinal ganglion cell has its origin in the retina and spreads into the into the brain forming the optic nerve. And it's a very long- it's a big cell. So the soma lives in the retina, while the axon lives in the central- pretty much in the central nervous system. And that makes it unique. And the main function of the ganglion cells, as you pointed out, transmit the signal from the retina to the brain.
Levi Sowers: So do- you've chosen to study this, this cable, if you will, the optic nerve. Does it get damaged in multiple types of disease? And you've mentioned three already, glaucoma, optic nerve itis and traumatic brain injury induced damage to it. So is it similar? Are the mechanisms or are there commonalities between these different types of eye diseases and retinal or optic nerve damage?
Oliver Gramlich: Yes and no. So what all those diseases have in common, they are vision threatening diseases. That's clear. Now. And so for various various reasons, let's start with glaucoma. So this is a disease- the second leading cause of blindness in the world, and this is particular due to the loss of those retinal ganglion cells that form below the optic nerves. And you probably have heard that elevated intraocular pressure. So where the pressure is higher in your eye and it should be is one of the main risk factors to develop glaucoma, that those cells die. It is not the main reason glaucoma has a multi-factorial pathology with all kinds of different things and we do not really know or pinpoint, hey, this is the main driver of the disease. It's a collection of certain factors that come together. So this is why we need preclinical research, because we do not exactly know. We have a clue or multiple clues, but we cannot pinpoint to to the to the dominant mechanism, if you will call it like this. With optic neuritis, same thing happens. So this is a problem of the optic nerve, almost more problem of the retina or at the eye in optic neuritis. We have an information to the optic nerve. For example, in multiple sclerosis. Multiple sclerosis is an autoimmune disease where you have T cells that attack the sheath of those optic nerve axons. The myelin sheathe is, if you will, is the electrical insulation and if you damage those, then the axon will die and subsequently, within, the retinal ganglion cell die. So in this with regards to this disease, we have a pretty good idea what's going on with the path of biology, but we do not have a lot against it to reverse it, to avoid it and to repair the damaged myelin sheath and that. So there are two main aspects here. One is we need to protect the retinal ganglion cells in the retina- so neuroprotection and we need to protect the optic nerve from getting the demyelinated or damaged through inflammation. So that's a multiple sclerosis, but also common mechanisms.
Brandon Rea: Gotcha. So with glaucoma, you said one of the biggest risk factors is intraocular pressure, with how much pressure there is in the eye you’ll have retinal cell death. Is- are there multiple forms of glaucoma? Is all glaucoma the same? I guess, is what I'm asking.
Oliver Gramlich: Not really. Since it is a multifactorial disease, you have different forms of glaucoma. The most common form is primary open angle glaucoma. And that is the form that we particularly investigate here with our veterans. Or yet at the at in our research mission here with the VA. Then there are other forms which is called normal normal tension glaucoma. So you have all the vision, loss and characteristics that you can see while looking to the retina, but not with the risk factor of some intraocular pressure elevation. And that's the thing. Those are the two main forms. Then we have sarcomas that develop during time, for example, because of trauma, where you have certain conditions happen to the eye that qualify, that qualifies to be called glaucoma. We have some congenital glaucoma, so it is not my focus on of interest because they are mostly genetic factors. I'm more focused to the age related glaucoma as a kind of a broad umbrella.
Brandon Rea: So we have all these different causes of glaucoma or diseases or damage that can happen to the optic nerve. Are there any- what excites you most about, on the horizon, like treatments or fast-forward for remedying some of these issues?
Oliver Gramlich:I mean, this is this is great. If you have a list of compounds and some of them some of the compounds are really strange and you don't know really if this works or not. But then if you if you start investigating the effects of absurd compounds and then you see, hey, look at that animal, it had a glaucoma damage prior to that. It had vision loss or look at that animal that had multiple sclerosis, vision loss, and you apply the compound and they start recovering with vision. That is one of the- yes, that's the payback. And if it is, it actually works. And I mean, you know, this is rare. Those effects are rare most of the time. I don't I think more than 90% of those compounds that you have in mind, they fail and the percent that you that you get lucky with. These are the ones that you need to push forward. Try hard. And out of those 10% as maybe 1% that actually will go forward to a clinical application. So but if you if you have that is you are the person who found that one, that's an amazing feeling.
Levi Sowers: Yeah. So what specifically do you focus on in your research? So, Oliver, within the last couple years was a major player in a four year award from the VA. Can you tell us a little bit about that, what your focus is?
Oliver Gramlich: Yes, sure. So yeah, that was, that was quite great with, with, with the award that we got, we pretty much look at two different things. The first thing is to see is biomarkers of the visual system, like, for example, visual acuity or degeneration of the retina that you can investigate with an imaging device. So pretty much readouts that you have in the clinic to translate those readouts back to an animal model, then have the animal model and different treatments to see if we can measure treatment success with those readouts. And then trends. Latest forwards back to the clinic to see, Hey, we do have the same readouts. This works in the animal model, this particular compound. Now we can move forward. This is the grant in a nutshell. And with new compounds or new treatment strategies. One thing that we wanted to investigate is if we can enhance recovery in multiple sclerosis related optic neuritis through the combination of currently used drugs and, for example, specific diet. Yeah? So it's a specific diet change in lifestyle - changing what you eat combined with immunomodulatory drugs actually increases quality of vision and therefore quality of life.
Brandon Rea: So what kind of diet changes did we make medically when you said that? I thought of the old saying where carrots are good for your eyes, eat a bunch of carrots.
Oliver Gramlich: Yes, but have you ever seen a rabbit with glasses?
Brandon Rea: That's very true, yes.
Levi Sowers: That's awesome.
Oliver Gramlich: Well, yes. So the diets that we have that we can currently focusing on is a mediterranean diet. Of course, the other thing that we- that we look at is a high fat based diet, because those two things do particular particular routes with your with your metabolism. And depending on your condition, one metabolism pathway is better than the other when it comes to repels the mule in cheese. And we want to see if there are differences between one or another diet. The next thing is intermittent Fasting is very interesting because the body needs to switch between different fuels and to switch between the different fuels actually is neuroprotective and anti-inflammatory. And all those two things significantly contribute to a recovery of the visual system.
Levi Sowers: What are the readouts you use in animals to study these database changes in these disease settings?
Oliver Gramlich: So the two main readouts that we have is this as I said, copy and paste from, from clinical practice, we device that is called optical coherence two across. And what that thing does is if you go to the eye doctor and the eye doctor says, Hey, can you please look into this wide camera here? We probably all experience that. But what's on the other side is that the camera focuses on the retina and can do a three dimensional reconstruction of the retina. And what we can do with that is we can determine if, for example, delay in the retina where the ganglion cells live. So those cells that form the optic nerve gets thinner. And this is an indicator of disease progression, if you will, and if the is the retina ganglion. So they get thinner is an indicator on how well the visual system overall is with respect to that particular disease, the sedimentation. And if the slope of thinning over time is faster or slower. So you can estimate progression and the same thing, we can do the same thing in mice, same technique, of course, slightly alter it to set up, but we can actually exactly measure that over time and see, for example, the treatment halts thinning or that thinning never happens - that would be the ultimate goal, but there will be no regrowth of ganglion cells, unfortunately. So we need to protect what's there. That's the first big or major, major outcome parameter. The second one is visual acuity. So, for example, you sit there and the doctor says, “Hey, can you please read the sentence?” “Yes, of course. It is “MLK Y Y 2 5 0.” I mean, you can't do that with a mouse, yeah?
[laughter]
Oliver Gramlich: The mouse is gonna push a button and say, “Yeah, I can see that.”
Brandon Rea: Just for fun, You could ask the mouse.
Levi Sowers: I think, you know, we have the same- this brings up a really good point. And I think we have the same thing in migraine is you can't tell if a mouse has a migraine, right? The only thing we can do is get close to what migraine presents as in humans, and use them as models. And I think that's a really important point to make. And I feel like that's what you're doing here in this case.
Oliver Gramlich: That's correct. So we found we've found a way to measure visual acuity in a mouse without the mouse having push buttons. It's a reflex. And the mouse can either see it or it can't see it. And it is based on illumination and how good the object is that they have to look at. And this relates 1 to 1, to the clinic. So of course, we want to see if a drug we first want to see when we make the animal sick, that visual acuity drops. Then we apply the drop and visual acuity comes back up. That would be the ultimate goal. Then we know, okay, it works on on a functional level. While OCT, Optical Coherence Tomography, is a structural readout, Visual acuity is a functional readout.
Levi Sowers: In a most basic sense in research is really, to oversimplify it, there's a readout in terms of, I'm not sure how to put it. You know, you have a biological readout and then you have like a functional readout, if you will? Can you maybe discuss like what the difference between those two are and why one would maybe be more important or not more important for translational purposes? That's a really tough question. And I think something that I think is difficult to understand even for some scientists.
Oliver Gramlich: Yeah, it's absolutely- you are absolutely correct. That's what we are talking about right now. That's the theory in a in a perfect in a perfect world, you would see a and a structural improvement and this this should correlate with a functional improvement. Unfortunately, it's not the case. Sometimes you see a functional improvement, but no structural improvement. But this is absolutely fine. Yeah. If if we can increase function and preserve the structure, that's the goal. That's really the goal. As I said earlier, there is no way at the moment to bring back lost ganglion cells, but we need to work with what we have. And you cannot gain a structural improvement so much, but you can gain functional improvement. And so that's why we have different techniques to address, both to determine treatment success. If you then go into the into the optic nerve, the optic nerve is a thing that we cannot image that easily from the outside. And actually there we can focus on a structural recovery because of of let's to repair the myelin shear so the damaged coating of the axons of the nerve fibers and that is something we can assess unfortunately only post mortem or in the dish. Yeah. And not so much in a living organism at the moment. We are working on that to get those techniques as well. And this is another point why it is so important to look at the structures post mortem and then correlate what we see with the functional readouts.
Levi Sowers: Yeah, it's really fantastic. You know, another big question I have, in addition research, is like how when you have retinal loss and this is something that I've thought about a lot in all of our meetings that we have together. And when you guys present your research is when you get retinal ganglion loss and it's smaller. Obviously we need retinal ganglion cells to see right there fundamental like how much is the endpoint of those cells affected when you have cell loss? So does- is the visual cortex, which is I think the endpoint here, is that affected by the loss of the cells? Could it be a target of future treatments as well? I'm just curious.
Oliver Gramlich: I mean, the crosstalk, the crosstalk between the brain and eye is- it's not a one way street. Yeah. So of course, the visual information could get sent to the brain, but on the other hand, we need a lot of stuff in the retina so that the retina is healthy and most of the stuff comes from the brain and gets it gets transported via the optic nerve to the retina and vice versa. There are some some some stuff that needs to that the retina needs to get rid of, which then gets transported the other way. And those interactions in transport and that could these are all factors that are neuroprotective so that the retina really works as as it should be. And particularly the retinal ganglion cells. So if there's a problem in the brain, in the visual tract, you would see it in the retina.
Levi Sowers: Interesting. Okay.
Oliver Gramlich: And vice versa. If the retina doesn't work properly, you will see effects in the brain on the visual cortex, for example. And if for example and I may make this broad, but you probably know this is people that are blind or that are getting bombed, so the whole pathway in the brain degenerates over time because it's not used. So both both systems, the brain and the retina and the connection, which is the optic nerve between the two, which is the optic nerve, those those three things need to be to function.
Levi Sowers: Oliver, it's been a great interview. Thanks! So a couple of last questions. What do you do for fun? Or do you just live in science land all the time?
Oliver Gramlich: Well, from time to time, I need my air, my air therapy. This is when I’m done with work and looking at mice and rats and ganglion cells in the dish. I love to to get out on the motorcycle and ride the highways and the country roads. That's one thing that I really enjoy. Of course, you cannot do it in the Iowa winter.
Levi Sowers: No, no. That’d be a little adventurous, to say the least.
Oliver Gramlich: So in the wintertime it's more or less related to to two winter sports. So if I get a chance to get out for skiing, that is what I really, really enjoy.
Levi Sowers: You came to the wrong place for skiing.
Brandon Rea: It’s real easy skiing here.
Levi Sowers: Well, cross-country skiing.
Oliver Gramlich: It's very- it's better than nothing. But yeah.
Brandon Rea: Have you been watching the Winter Olympics?
Oliver Gramlich: Yes. It was kind of interesting. The the biathlon where you do cross-country skiing and shooting.
Levi Sowers: Yeah, pretty, pretty cool. Also, the Germans have been crushing all the sledding events, bobsled, skeleton, etc..
Oliver Gramlich: I mean, this is crazy about it. You jump on to that little metal thing and go downhill. And what is it, a 140 miles an hour?
Levi Sowers: It's really really fast. It's scary, in my opinion.
Brandon Rea: Yeah. Yeah. You just hold on for dear life.
Levi Sowers: And my last last question, what's your favorite movie?
Oliver Gramlich: So that's a tough question.
Levi Sowers: This is the toughest question you've answered all day.
Oliver Gramlich: My what's my favorite movie?
Levi Sowers: You've already thought about it too long.
Oliver Gramlich: I thought about it, too. It's too long. So at the moment, I don't really have time to watch a whole lot of movies.
Levi Sowers: That's fair. Yeah. I don't watch many movies either anymore. That's okay. Well, hey, that's okay. You don't have to answer. And also, thanks a lot for coming on the best podcast to really appreciate it. I think you've really informed as well about what you study and why you study it so awesome. Thank you.
Oliver Gramlich: I have to thank you too for the invitation. And I hope even with my strange accent that I, that I was able to to explain everything correctly, thank you very much!
Announcer: This concludes today's Vets First Podcast. For questions or comments relating to the program, please direct email correspondence to vetsfirstpodcast@gmail.com. Thanks for listening!